Effect of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density

A Phase 2, Randomized, Double-blinded, Placebo-controlled, Dose-Response Study of Oral (Z)-Endoxifen in Premenopausal Women With Measurable Breast Density

This is a randomized, double-blinded, placebo-controlled dose-response efficacy study of oral (Z)-endoxifen in premenopausal women with measurable breast density. There will be 5 in-clinic visits (Screening, Day 1, Months 1, 3 and 6) and 3 self-report visits (Months 2, 4 and 5). Standard of care mammograms will be used for the screening mammogram as well as the 24-month follow up visit.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Density
• Intervention / Treatment: Drug: Placebo; Drug: Z-Endoxifen

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Heather Fraser, PhD; Phone Number: 206-707-3088; Email: heather.fraser@atossainc.com

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karma Study Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Premenopausal women (defined as having at least one menstruation during the prior 12 months; women with an intrauterine device are considered premenopausal if <52 years)
2. Women of childbearing potential using a highly effective method of birth control* throughout the study period and willing to comply with monthly pregnancy testing
3. Screening mammogram performed within 3 month of study inclusion
4. Mammographic density assessed as BI-RADS® score B, C, or D
5. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects

Exclusion Criteria:

1. Mammographic BI-RADS® malignancy code ≥3 at baseline mammography
2. Any previous diagnosis of breast cancer, including carcinoma in situ, or any other cancer (non-melanoma skin cancer and in situ cancer of the cervix are not exclusion criteria)
3. A history of breast surgery, e.g., reduction or enlargement, which might affect mammographic density measurements

4. Current medical conditions:

   1. APC (activated protein C) resistance, an inherited coagulation disorder
   2. Systolic pressure higher than 160 mm Hg or diastolic higher than 100 mm Hg
   3. Cataract(s)
   4. Uncontrolled diabetes (defined as HbA1c >50 mmol/mol)
   5. Abnormal lab values deemed clinically significant by Investigator
5. BMI > 30
6. Women who have an increased risk of venous thrombosis due to immobilization, e.g., using wheelchair

7. Agents that have the potential to decrease endoxifen levels through increased metabolic clearance:

   1. Certain anti-epileptic therapies (carbamazepine, fenytoin, fenobarbital, lamotrigine)
   2. Certain antibiotics (rifamycins)
   3. St John's wort (in Swedish: johannesört)
   4. Certain HIV medications (efavirenz, ritonavir)
8. Lactating, pregnant, or plan to become pregnant in the next year
9. History of thromboembolic disease such as embolus, deep vein thrombosis, stroke, TIA (transient ischemic attack) or myocardial infarction
10. Allergy to endoxifen or any of its components
11. Previous treatment with an anti-oestrogen, including experimental drug studies (e.g., Karma CREME, Karisma-1 or Karisma-2)
12. Prescribed and regular use of anticoagulants (defined as substances included in group B01A in the ATC-system)
13. Participation in another investigational clinical trial in the last 6 months
14. Not willing or able to understand the study information and/or informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; oral capsule	Drug: Placebo; Placebo
Experimental: 1 mg (Z)-endoxifen; oral capsule	Drug: Z-Endoxifen; Z-Endoxifen
Experimental: 2 mg (Z)-endoxifen; oral capsule	Drug: Z-Endoxifen; Z-Endoxifen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mammographic density area (cm2) assessed by iCAD® software	Change from baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of mammographic density area (cm2) assessed by iCAD® software	Change from baseline	3 months
Change of mammographic density area (cm2) assessed by Stratus software	Change from baseline	6 months
Change of mammographic density area (cm2) assessed by Stratus software	Change from baseline	3 months
Change from baseline responses to the Breast Cancer Prevention Trial Eight Symptom Scale (BESS)	5-point Likert-type scale	6 months
Comparison of adverse events	assessment of adverse events	6 months

Collaborators and Investigators

• Sponsor: Atossa Therapeutics, Inc.
• Investigators: Study Director: Steven Quay, MD, Atossa Therapeutics, Inc.; Principal Investigator: Per Hall, MD, Södersjukhuset, Stockholm, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2021
• Primary Completion (Estimated): August 28, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: ATOS-016R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No